Hepatitis B virus mutations in the pre-S genome before and after liver transplantation

Mutational changes in the pre-S region of hepatitis B virus (HBV) were analyzed in 20 patients who experienced HBV reinfection after orthotopic liver transplantation (OLT), HBV DNA was extracted hom patient sera before and after OLT. The pre-S sequence was amplified via polymerase chain reaction, subcloned, sequenced, and analyzed. In 18 of 20 patients, mutational changes were found in the pre-S region pre- or post-OLT; 11 showed point mutations (1-10) and 7 cases major changes (insertions/deletions). For the point mutations, there was no trend in the selection of wild-type (wt) HBV before or after OLT in the pre-S region. Additional HBV reinfection during hepatitis B surface antigen antibody (anti-HBs) administration had no influence on selection pressure in the pre-S region, In contrast, insertions/deletions were more frequently found before OLT, In the 7 patients with deletions/insertions, changes in the hepatocyte attachment site were not seen after OLT, Interestingly, the only patient with changes in a major virus population after OLT had changes in the CCAAT-box of the S-promoter, As shown by gel shift analysis, this mutation was associated with loss of specific binding to this element and thus probably led to dysregulation of S gene transcription, Major changes in the pre-S genome are mainly seen before OLT, and HBV reinfection does occur with the intact hepatocyte attachment sites after OLT, Anti-HBs (hepatitis B immune globulin [HBIg]) creates no selection pressure on the pre-S region. The mutation in the CCAAT-box of the S-promoter potentially leads to its dysregulation and may be associated with the occurrence of fibrosing cholestatic hepatitis after OLT.